chr19-13962826-G-T

Variant names:

• chr19-13962826-G-T
• rs1385084150
• NM_002918.5:c.2809C>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002918.5(RFX1):​c.2809C>A​(p.Leu937Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000458 in 1,527,530 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000044 (0 hom.)
• Consequence: RFX1 NM_002918.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.06
• Publications: 1 publications found

Genes affected

RFX1 (HGNC:9982): (regulatory factor X1) This gene encodes a member of the regulatory factor X (RFX) family of transcription factors, which are characterized by a winged-helix DNA-binding domain. The encoded transcription factor contains an N-terminal activation domain and a C-terminal repression domain, and may activate or repress target gene expression depending on cellular context. This transcription factor has been shown to regulate a wide variety of genes involved in immunity and cancer, including the MHC class II genes and genes that may be involved in cancer progression. This gene exhibits altered expression in glioblastoma and the autoimmune disease systemic lupus erythematosis (SLE). [provided by RefSeq, Jul 2016]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06452495).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RFX1	NM_002918.5	c.2809C>A	p.Leu937Met	missense_variant	Exon 21 of 21	ENST00000254325.9	NP_002909.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RFX1	ENST00000254325.9	c.2809C>A	p.Leu937Met	missense_variant	Exon 21 of 21	1	NM_002918.5	ENSP00000254325.3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152148 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000237 AC: 3 AN: 126760 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000288

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000436 AC: 6 AN: 1375264 Hom.: 0 Cov.: 35 AF XY: 0.00000295 AC XY: 2 AN XY: 677544

African (AFR) AF: 0.00 AC: 0 AN: 31302

American (AMR) AF: 0.00 AC: 0 AN: 34098

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24420

East Asian (EAS) AF: 0.000141 AC: 5 AN: 35526

South Asian (SAS) AF: 0.0000129 AC: 1 AN: 77694

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36440

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5646

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1072768

Other (OTH) AF: 0.00 AC: 0 AN: 57370

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152266 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74454

African (AFR) AF: 0.00 AC: 0 AN: 41564

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67990

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 18, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2809C>A (p.L937M) alteration is located in exon 21 (coding exon 20) of the RFX1 gene. This alteration results from a C to A substitution at nucleotide position 2809, causing the leucine (L) at amino acid position 937 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	20
DANN	Benign	0.94
DEOGEN2	Benign	0.076	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.55	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N
PhyloP100		1.1
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.045
Sift	Benign	0.17	T
Sift4G	Benign	0.32	T
Polyphen		0.070	B
Vest4		0.15
MutPred		0.19		Loss of loop (P = 0.0288);
MVP		0.22
MPC		0.89
ClinPred		0.053	T
GERP RS		3.5
Varity_R		0.19
gMVP		0.14
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1385084150; hg19: chr19-14073638;